Bile acids are involved in a variety of physiological and pathological processes of the hepatobiliary and gastrointestinal systems. This project aims to study the effects of bile acids on the hepatobiliary system with particular reference to the following: 1) hepatotoxicity and cholestatic effect of lithocholic acid (LCA) and chenodeoxycholic acid (CDA), 2) protective effect of cholic acid (CA) against the cholestatic and hepatotoxic effects of LCA and CDA, 3) evaluation of possible species difference in the effects of bile acids on the hepatobiliary systems. We intend to use rats, hamsters and guinea pigs of both sexes with or without bile fistula. Bile acids (salts) will be administered intravenously either singly or in combination (in order to evaluate the antagonistic effect of CA against LCA and CDA) and their effects will be assessed by 1) the rate of biliary excretion, 2) the light and electron microscopy (both transmission and scanning) of the liver including enzyme histochemistry and freeze etching techniques, 3) qualitative and quantitative analysis of bile acids in bile (e.g. gas-liquid chromatography, and 4) estimation of serum bilirubin, glutamic pyruvate transaminase and 5' nucleotidase. We also plan to run subacute (up to 3 weeks) and chronic (longer than 3 weeks) dietary experiments in which LCA and CDA is administered. In some of the above experiments, suppression of the intestinal bacterial flora by antibiotics will be tried in order to simulate a "germ-free" state, so the the effects of CDA may be assessed more accurately than in conventional animals.